The ultimate goals of this research are to characterize the forces directing RNA folding, and to use this knowledge to reliably predict RNA structure from sequence and to suggest lead compounds for therapeutics targeting RNA. Insights into the role of electrostatic interactions in directing RNA folding will be provided by thermodynamic and NMR structural studies of duplexes containing isoC-isoG base pairs. A hypothesis for providing selective formation of AU and GU base pairs by antisense agents will be tested with oligonucleotides containing 2- thiouridine and 4-thiouridine. Binding will be measured to short oligonucleotides and to a group I ribozyme derived from mouse Pneumocystis carinii. The results will lay a foundation for facilitating discovery of therapeutics based on RNA sequence information.